Abstract
Although a physiological role for redox signaling is now clearly established, the processes sensitive to redox signaling remains to be identified. Ratiometric probes selective for H2O2 have revealed its complex spatiotemporal dynamics during neural development and adult regeneration and perturbations of H2O2 levels disturb cell plasticity and morphogenesis. Here we ask whether endogenous H2O2 could participate in the patterning of the embryo. We find that perturbations of endogenous H2O2 levels impact on the distribution of the Engrailed homeoprotein, a strong determinant of midbrain patterning. Engrailed 2 is secreted from cells with high H2O2 levels and taken up by cells with low H2O2 levels where it leads to increased H2O2 production, steering the directional spread of the Engrailed gradient. These results illustrate the interplay between protein signaling pathways and metabolic processes during morphogenetic events.
Highlights
A physiological role for redox signaling is clearly established, the processes sensitive to redox signaling remains to be identified
We have previously shown that the zebrafish midbrain–hindbrain boundary (MHB) displays high levels of H2O2 that cannot be lowered without affecting tectum topography[6], a process that requires the graded distribution of the Engrailed HPs (EN in amniotes, Eng in fish)[15,16,17,18]
H2O2 levels increased over time (Fig. 1e), but with a marked gradient from the MHB to the most anterior part of the tectum (Fig. 1d)
Summary
A physiological role for redox signaling is clearly established, the processes sensitive to redox signaling remains to be identified. Ratiometric probes selective for H2O2 have revealed its complex spatiotemporal dynamics during neural development and adult regeneration and perturbations of H2O2 levels disturb cell plasticity and morphogenesis. Engrailed 2 is secreted from cells with high H2O2 levels and taken up by cells with low H2O2 levels where it leads to increased H2O2 production, steering the directional spread of the Engrailed gradient. These results illustrate the interplay between protein signaling pathways and metabolic processes during morphogenetic events. Engrailed is released from cells with high H2O2 levels and transfer to cells with low H2O2 levels in which it stimulates H2O2 production, thereby controlling its own polarized traffic. We identify cysteine 175 as a key residue in the redox regulation of Engrailed traffic
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